SIGNAL TRANSDUCTION FROM THE T-CELL ANTIGEN RECEPTOR

描述(改编自申请者摘要)：分子的级联 将细胞表面配体-受体相互作用与调控联系起来的事件 人们对细胞功能的变化只有部分了解。T细胞 抗原受体(TCR)是包括CD3在内的多聚体复合体。 作为主要识别和信号转导的复合体 在特定的T细胞激活过程中。通过以下方式触发TCR 激活配体刺激多效性激活反应，最终达到 在细胞生长和分化方面。典型的早期(分钟) 对TCR结扎的反应是胞质颗粒的胞吐作用 细胞溶解T淋巴细胞(CTL)。 该项目的长期目标是定义 TCR连接启动跨膜信号的产生和传播。 最近的研究表明，一种未定义的蛋白酪氨酸激酶可以作为 配体结合的TCR.A关键信号转导元件 这种TCR偶联蛋白酪氨酸激酶的底物是磷脂酰肌醇- 特异性磷脂酶C(PLC-Gamma1)。这项建议的具体目的 主要内容如下：(1)鉴定蛋白酪氨酸激酶 将TCR连接与PLC-Gamma1的酪氨酸磷酸化偶联；(2) 确定PLC-Gamma1同工酶表达改变对信号的影响 通过TCR的转导；以及(3)研究蛋白质的作用 酪氨酸激酶活化和p21ras在TCR依赖性颗粒胞吐中的作用 在细胞溶解的T细胞中。调查人员表示，这一结果 研究应为跨膜信号机制提供新的见解 参与正常的细胞生长和细胞转化。

DESCRIPTION (Adapted from applicant's abstract): The cascade of molecular events that link cell surface ligand-receptor interactions to regulated changes in cellular functions are only partially understood. The T-cell antigen receptor (TCR) is a multimeric complex, which includes the CD3 complex that serves as the primary recognition and signal-transducing element during specific T-cell activation. Triggering of the TCR by activating ligands stimulates a pleiotropic activation response culminating in cell growth and differentiation. A prototypical early (minutes) response to TCR ligation is the exocytosis of cytoplasmic granules from cytolytic T-lymphocytes (CTL). The long-term goals of this project are to define the mechanisms of transmembrane signal generation and propagation initiated by TCR ligation. Recent studies indicate that an undefined protein tyrosine kinase serves as the proximal signal-transducing element from ligand-bound TCR.A critical substrate for this TCR-coupled protein tyrosine kinase is phosphoinositide- specific phospholipase C (PLC-gamma1). The specific aims of this proposal are the following: (1) To identify the protein tyrosine kinase that couples TCR-ligation to the tyrosine phosphorylation of PLC-gamma1; (2) to determine the effect of altered PLC-gamma1 isozyme expression on signal transduction through the TCR; and (3) to examine the role of protein tyrosine kinase activation and p21ras in TCR-dependent granule exocytosis in cytolytic T-cells. The investigator indicates that the results of this study should offer novel insights into transmembrane signalling mechanisms involved in both normal cell growth and cellular transformation.